A sensitive, rapid and specific liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for quantification of gabapentin in human plasma has been developed. After a single plasma protein precipitation with methanol, gabapentin and metformin (internal standard) were chromatographed on a Inertsil ODS-3 column (50 mm x 2.1 mm ID, 3 microm) with mobile phase consisting of methanol-0.2% formic acid aqueous solution (80:20, v/v) at a flow-rate of 0.2 mL x min(-1). Electrospray ionization (ESI) source was applied and operated in the positive ion mode. Multiple reaction monitoring (MRM) mode with the transitions of m/z 172 --> m/z 154 and m/z 130 --> m/z 71 were used to quantify gabapentin and metformin, respectively. The run time was 2.2 min. The linear calibration curve was obtained in the concentration range of 40.8-8.16x10(3) ng x mL(-1). The lower limit of quantification was 40.8 ng x mL(-1). The intra- and inter-day precision (RSD) was less than 12%, and the accuracy (RE) was within +/-6.4% calculated from quality control (QC) samples. The method was used to determine the concentration of gabapentin in human plasma after a single oral administration of 600 mg gabapentin capsule to 20 healthy male Chinese volunteers. The method was proved to be selective, sensitive, rapid and suitable for pharmacokinetic study of gabapentin in human plasma.

Objective To explore the clinical and neuroimaging features of a frontotemporal dementia with parkinsonism linked to chromosome 17 ( FTDP-17 ) pedigree caused by mutation of microtubule-associated protein tau ( MAPT) gene.Methods The proband and one patient from a FTDP-17 pedigree were assessed through standardized clinical evaluation , neuropsychology assessment , video-electroencephalogrom ,MRI, genetic sequencing , as well as 18 F fludeoxyglucose ( FDG) SPECT for brain metabolism and 11 C 2β-carbomethoxy-3β-( 4-fluoro ) tropane ( CFT ) PET for dopamine transporter ( DAT ) distribution, respectively.Results A FTDP pedigree with 15 patients (6 still alive) was recruited to this study.The proband and one affected patient were genotyped and confirmed as MAPT c .1788T>G mutation. Parkinsonism was the first symptom for both two patients . Personality, speech changes and dementia accompanied with brain atrophy were developed at the later stage in one patient .The 18 F FDG SPECT studies illustrated asymmetric hypometabolism of the temporal , frontal lobes and basal ganglia in two patients . Regarding to the 11 C CFT PET, one affected patient showed asymmetric decreased uptake of tracer in basal ganglia regions.Conclusions FTDP-17 can display a confusingly broad clinical phenotype , with the parkinsonism as the first symptom . Brain glucose metabolism and DAT distribution could be potential biomarkers in early diagnosis of FTDP-17.

Orally disintegrating tablets (ODT), a kind of new solid tablet that rapidly disintegrates to work in the mouth, has became the hot form of new drug research in recent years with many advantages, such as the convenient taking, a widely applicable people, fast acting, high bioavailability, good compliance, and so on. ODT has been widely used in chemical medicines, while the application of it in traditional Chinese medicines (TCMs) is still in the stage of development The development of TCMs ODT provides a new direction for the research of Chinese medicine new dosage, accelerates the pace of connecting to the world and modernization of Chinese medicine. This dosage has a broad market prospect, and its quality control and assessment standards, taste, the disintegration time in vitro and evaluation method are the key factors that affect the industrialization, standardization of Chinese medicine ODT. Therefore, this paper reviewed the characteristics, preparation, taste masking technology and quality evaluation with new technology of ODT. Meantime, numerous application examples of ODT used in traditional Chinese medicine were described. We expect to provide the reference and utilization for the development of traditional Chinese medicine orally disinteeratine tablets.
Administration, Oral ; Drug Compounding ; methods ; Humans ; Medicine, Chinese Traditional ; Solubility ; Tablets ; administration & dosage ; chemistry ; Taste

AIM:To observe the structural basis of ocular motility abnormalities in patients with congenital fibrosis of the extraocular muscles type Ⅰ ( CFEOM Ⅰ) due to missense mutations in the developmental kinesin KIF21A using high - resolution magnetic resonance imaging ( MRI) .
METHODS: Totally 11 affected individuals reported KIF21A mutations were correlated with MRI studies demonstrating extraocular muscles ( EOMs ) size, location, contractility, and innervation. EOMs and the motor nerve in the orbits were imaged with T1 weighted in a triplanar scan using a dual-phased coils with 2. 0mm thick. Motor nerves were imaged at the brainstem using head coils and 3D-FIESTA with 0. 6-mm thick.
RESULTS: Patients with CFEOM Ⅰ exhibited different degrees of hypoplasia of oculomotor nerve, the abducens nerve and the trochlear nerve were also affected, of which 8 cases of orbital section could see the signal of abnormal nerve dominated by oculomotor nerve to lateral rectus. The both sides of six EOMS in all patients exhibited variable atrophy and abnormal bright internal signal on T1 imaging, particularly severe for the superior rectus and levator muscles.
CONCLUSION: High - resolution MRI can directly demonstrate pathology of motor nerves,affected EOMs, and ‘Pulley' hypoplasia caused by CFEOM Ⅰ due to mutations in KIF21A,and these findings suggest that the neuronal hypoplasia is the etiological factor of CFEOM.

Objective To investigate the changes and significance of concentration of soluble intercellular adhesion molecule-1(sICAM-1) in cerebrospinal fluid (CSF) of bacterial meningitis(BM) in rabbits. Methods A total of 36 rabbits were randomly divided into m eningitis group, meningitis cefotaxime-treated group and control group. BM indu ced by escherichia coli(Ec) via cerebellomedullary cistern inoculated. Normal sa line was injected in control group. CSF was sampled in different time. The conce ntration of CSF sICAM-1 was detected by ELISA.Results 1.There was a low concentration of sICAM-1 in CSF in 85 percent of normal rabbi ts.2.In meningitis group, there was a sharp rise in the concentration of CSF sIC AM-1 at 6 hours after Ec was inoculated, reached a peak level at 12 hours, and t here was higher concentration of CSF sICAM-1 between 6 and 24 hour than that at 0 hour.3.In meningitis cefotaxime-treated group, the concentration of CSF sICAM -1 at 6 hour and 12 hours was similar to meningitis group, the time that get pe ak level was at 24 hours that at 12 hours after making use of antimicrobial agen t.The peak level was higher than meningitis group. The concentration of CSF sICA M-1 decreased markedly at 48 hours that made use of antimicrobial agent 36 hour s later,but the concentration was still higher than the peak level of meningitis group.Afterwards, with the time of making use of antimicrobial agent lengthened ,the concentration of CSF sICAM-1 decreased gradually.4.Experimental results in dicated by correlating analysis to these data that there was positive correlatio n in the concentration of CSF sICAM-1 with the brain water content.Conclusions sICAM-1 participates in the pathological process of BM, and contributes to the damage of blood brain barrier and the formation of brain edema.There is importan t significance that drugs which can resist the discharge of sICAM-1 will be impl ied. J Appl Clin Pediatr,2005,20(2):163-165

Objective To retrospectively evaluate the mammographic features of breast ductal carcinoma in situ (DCIS)and DCIS with small invasive foci,and to analyze the correlation between the mammographic findings and the prognostic biologic factors.Methods The mammographic examination was performed in 95 consecutive women with breast DCIS(n = 50)and DCIS with invasive foci(n = 45 ).The prognostic biologic factors including progesterone receptor(PR),C-erbB-2,and p53 were evaluated in 62 of 95 cases.Categorical data were expressed as percentages and analyzed by using the X~2 test,and furthermore the odds ratio was measured.Results(1)Only one abnormality was seen on mammography in 62 patients. Combined two abnormalities on mammography were seen in 26 patients.Mammograms were normal in 7 patients.(2)Calcifications with or without other abnormality were noted in 62 cases.Of them,73% (n =45)had higher probability of malignancy calcifications and the others were intermediate concern calcifications.Clustered calcifications(36 lesions)was the most common distribution,which usually accompanied by another abnormality.And then were segmental(18 lesions)distributed pattern.As far as the shape of mass (n = 22)was concerned,the oval shaped lesion(13 cases)was the most common,and the margin of the mass appeared as ill-defined in 15 eases,microlobulated in 1,circumscribed in 4,and obscured in 2,respectively.Isodensity mass had a higher frequency in this group(12/22,55%).Other non-calcification findings included architecture distortion(7 cases),local asymmetry (15 cases),global asymmetry (5 cases),and solitary dilated duct (3 cases),and most of them accompanied with other signs. (3)For expression profile of the biological factors,significant differences were found among malignant calcification group,intermediate concern calcification group,and non-calcification group. The odds of PR positive for the lesions noted as non-calcification were 11.00 times higher (X~2 =8.571 ,P=0.003 ;95% CI, 1.998—60.572)than the lesions noted as intermediate concern calcifications,and 8.80 times higher (X~2 = 9.748,P=0.002 ;95% CI,2.024—38.253)than the lesions noted as malignant calcifications.The odds of C-erbB-2 positive for the lesions showed as malignant calcifications were 12.35 times higher (X~2=7.353, P=0.007 ;95% CI,1.447—105.443)than the lesions showed as non-calcification,and 5.74 times higher (X~2=4.977,P = 0.026;95% CI,1.110—29.645)than the lesions showed as intermediate concern calcifications.Conclusion The mammographic features of DCIS and DCIS with small invasive foci were characteristic.Mammographic findings could be a prognostic markers,which could provide a possibility for making a treatment plan.

AIM: To investigate the dynamic variety of frequency and function of FoxP3~+ regulatory T cells in patients with acute hepatitis B (AHB). METHODS: Peripheral blood mononuclear cells (PBMCs) from 15 AHB patients at acute phase (week 1 of illness), convalescent phase (primary occurrence of both ALT level normalization and HBsAg negative conversion), resolved phase (at least 8 weeks after both ALT normalization and HBsAg seroconversion, and 15 health subjects were analyzed for FoxP3 (Forkhead/winged helix transcription factor) mRNA expression in MACS magnetic beads-purified CD4~+ T cells by real-time RT-PCR assay. The effects of Treg cells on the proliferation of CD4~+CD25~- T cells were examined by a ~3[H]-thymidine incorporation assay. RESULTS: AHB patients presented a significantly higher FoxP3 mRNA expression at convalescent phase than acute phase (t=-6.04, P<0.01) and resolved phase (t=4.45, P<0.01), and healthy controls (t=3.44, P<0.01). We also observed that the suppression efficiency of Treg cells on proliferation of CD4~+CD25~- T cells was lower at acute phase than convalescent phase (t=-5.30, P<0.01) and resolved phase (t=-3.20, P<0.05), but there was no significant difference between healthy controls and any phase of AHB. CONCLUSION: AHB patients presented lower circulating Treg frequency and suppression function at acute phase, and both of them are increased at convalescent phase, and then return to normal level along with disease resolved. This follow-up study furthers our understanding of Treg' s role in immunopathogenesis of hepatitis B.

The study on the pharmacokinetics of traditional Chinese medicines (TCMs) is a linking science during the modernization of TCMs, and plays an important role in the studies on the complex material base of TCMs, the in vivo process of ingredient/ component and the pharmacokinetics-pharmacodynamics correlation. However, because of the multi-ingredient/component system of TCMs, how to scientifically reveal the pharmacokinetics that is consistent with TCMs' characteristics has long been a hotspot and difficulty for the exploration. The optimal composition structure of the material basis of TCMs shows the best efficacy, while the difference between the multi-ingredient/component composition structures in the efficacy is closely related to their absorption, transport, metabolism and excretion in vivo. In this article, the authors systematically review the study methods for pharmacokinetics of TCMs and their compounds, and explore the pharmacokinetics of TCMs based on the "component structure theory". As a result, the method for integrating TCM component structure and the TCM pharmacokinetics was proposed to be adopted to intensively study the effect of the component structure on the in vivo TCM multi-ingredient/component pharmacokinetic characteristics, in order to promote the TCM modernization and innovation in China.
Animals ; Area Under Curve ; Chemistry, Pharmaceutical ; Humans ; Medicine, Chinese Traditional ; methods ; Pharmacokinetics ; Structure-Activity Relationship

Objective To explore the characteristics and data collection sources of featured literature databases in universities/colleges in Yunnan in order to provide evidence for building featured literature databases. Methods Key information about three types of featured literature databases was retrieved online, which included those being constructed jointly by some universities or colleges in Yunnan, owned by universities or colleges in Yunnan, and already in use in China Academic Library and Information System ( CALIS) , respectively. Comparison was performed among these featured literature databases in regard to data characteristics and collection sources. Results Among all the featured databases being constructed, 58.8% were based on literature on local resources, 17.6% on disciplines and specialties, and 11.8% on library literature. In-use featured databases in Yunnan were mainly based on local resources and disciplines, and the data were collected within their own organizations or through multi-sources. The featured databases in CALIS were of local resources, disciplines, and people, while their data were collected mainly within their own organizations, through other organizations and multi-sources. Conclusion Yunnan featured databases are of unique characteristics, but more should be done to define Yunnan style data, while it is necessary to collect data from a wider range of sources.

objective To explore the correlation of single nucleotide polymorphism (SNP) frequency of adiponectin(APN)in patients with type Ⅱ diabetes(T2DM)and its complications,investigate whether the SNP is a risk factor of inheritance of T2DM,and to set up a highly efficient.accurate, economical and practical screening assay to detect the mutation of APN in clinical practice.Methods According to the diagnostic criteria of T2DM,patients with coronary heart disease(CHD),hypertension (HP),and diabetic nephropathy(NE)were recruited into this study.In simple,12DM group,T2DM-HP, T2DM-CHD.T2DM-NE and the control group.serum biochemistry items are measured.The technique of denaturing high-performance liquid chromatography(DHPLC)was used to detect SNPs of ANP gene.Results After all fragments amplified in the reglen of promoter of APN gene were compared with APN GeneID:9370 sequence recorded in GenBank,point mutation has been identified(-11377G/C).The frequency of genotypes of GG,GC,and CC are 5.16%,42.25%,52.58%and 3.4%.32.75%,63.85%,respectively in the groups of T2DM and control.The frequency of G allele was related to the incidence of T2DM,and is a risk factor of T2DM.The relative risk of GC to CC in developing T2DM is much high than that in the control group (OR=0.55).By comparing the clinical data of different groups of genotype in T2DM,it was observed that the genotype affected systolic blood pressure,BMI,abdominal circumference, and waist-buttock ratio(P=0.015).After optimizing the experimental conditions.it was found column temperature 6 0℃ was the best when using DHPLC technology to estimate SNP of APN gene.Conclusion SNP (-11377G/C) of APN gene G allele has a definite correlation with complications of hypertension in T2DM patients,and may contribute to the genetic risk for type 2 diabetes.